Research ReportDopaminergic axons preferentially innervate dendritic spines with hyperactive glutamatergic synapses in the rat striatum

Dopaminergic and glutamatergic afferents simultaneously innervate median spiny neurons (MSNs) and interact to mediate basal ganglia functions. However, the association between dopaminergic and glutamatergic axons is not clear. In the present study, nigrostriatal, corticostriatal, and thalamostriatal axons were anterogradely traced with biotinylated dextran amines (BDA) in rats, and MSNs were labeled with chloromethylbenzamido-DiI for neurogeometric analysis. Results showed that nigrostriatal, but not corticostriatal or thalamostriatal, axons were biased to a target on dendritic spines of the MSNs. In addition, the MSN dendritic spines, which were innervated by tyrosine hydroxylase-immunoreactive (TH-IR) axons and vesicular glutamate transporter 1 or 2-immunoreactive (VGluT-IR) terminals, were significantly larger than dendritic spines innervated by VGluT-IR terminals alone. Under electron microscopy, glutamatergic synapses on the dendritic spines were located with TH-IR terminals and displayed longer postsynaptic density. In addition, these synapses were more perforated than those on dendritic spines lacking innervated TH-IR terminals. These results demonstrated that dopaminergic axons were biased to a target and preferred to innervate dendritic spines with hyperactive and high-efficacy glutamatergic synapses in the striatum.

► Gluergic and DAergic axons proportionally innervate MSN dendritic spines. ► DAergic axons were biased to a target on dendritic spines of the MSNs. ► Gluergic synaptic activity could influence the DAergic axonal distribution.